a) Field of the Invention
This invention relates to novel chromene derivatives and salts thereof, and specifically chromene derivatives and salts thereof, which have inhibitory action against the formation of advanced glycation end-products (AGE) and are useful as pharmaceuticals for the prevention and treatment of various adult diseases, especially diabetic complications, and also to pharmaceuticals containing them as effective ingredients.
b) Description of the Related Art
A diabetic also tends to develop at a high incidence one or more diabetic complications such as cardiovascular diseases, nephropathy, blindness and/or neuropathic aches, although the mechanisms of their developments have not been elucidated. In recent years, however, both abnormality in polyol pathway and sthenia of glycation have been attracting increasing attention as dysbolism induced by high blood glucose levels. Further, it has recently become increasingly evident that the reaction between amino compounds and reducing sugar, said reaction being known in the field of food chemistry, that is, the Maillard reaction proceeds in the living body to glycosylate a surprisingly wide variety of bioproteins and is strongly associated with causes for adult diseases, such as diabetes, and aging. It has been ascertained that this Maillard reaction on the living body results in the gradual formation of advanced glycation end-products (AGE) through complex intramolecular reconstitution. Accumulation of AGE in the body reduces the inherent functions of individual proteins, and is accordingly considered to be one of causes for diseases induced by such reductions, for example, diabetic complications, arteriosclerosis and aging-related diseases such as retinopathy, nephropathy, cardiovascular diseases, neurosis and cataract.
Under continued high blood glucose conditions like diabetes or by aging, many of bioproteins are considered to be subjected to glycation. Among such bioproteins, especially those slow in turnover, for example, collagen, free lens crystallin which does not undergo any turnover, and the like have been proven to undergo the latter-stage Maillard reaction.
As therapeutics for adult diseases, especially diabetic complications, said therapeutics having been developed by paying attention to the Maillard reaction on the living body, the compounds disclosed in JP kokai 9-40626 and JP kokai 9-59233 have been reported but nothing has been put on the market yet. Only aminoguanidine is in the stage of clinical tests.